Design,Synthesis And Antifungal Activity Of Novel Thiazole Derivatives As Fungicides

Plant diseases have been regarded as a threat for food security and crop production in our country in recent years.To develop novel thiazole compounds as agricultural fungicide,36pyrazole-thiazole carboxylate derivatives（Experiment A,Chapter 2）and 36 benzoic acid-thiazole ester derivatives（Experiment B,Chapter 3）were designed and synthesized in the experiment.The synthesized compounds were evaluated for in vitro antifungal experiment,scanning electron microscopy,molecular docking.In experiment A,fluxapyroxad was selected as a lead compound,and three series ofpyrazole-thiazole carboxylate derivatives were designed by bioisosterism.The target compounds were tested for in vitro bioactivity against eight agricultural fungi,including Botrytis cinerea and Valsa mali.The in vitro antifungal activity experiment results demonstrated that most of pyrazole-thiazole carboxylate derivatives showed excellent inhibitory activity against Botrytis cinerea and Valsa mali.Among all the synthesized pyrazole-thiazole carboxylate derivatives,compound A15 displayed the best inhibitory effect against Valsa mali(EC₅₀=0.32 mg/L).These scanning electron microscopy observations revealed that compound A15 caused a certain degree of damage to the cell wall of Valsa mali.Compound A24 displayed the best inhibitory activity against Botrytis cinerea and Sclerotinia scleotiorum,with EC₅₀ values of 0.40 and 3.54 mg/L respectively.Compound A3 showed remarkable antifungal activity against Botrytis cinerea and Valsa mali,with EC50 values of 0.77 and 0.67 mg/L respectively.Based on experiment A,pyrazole fragment of pyrazole-thiazole carboxylate derivatives was replaced with benzene ring in experiment B.First,compound B1-B9 were tested for preliminary antifungal activity screening.Experiment results demonstrated that compounds with isopropyl,3-chlorophenyl or 3-methyl phenyl at R¹ position displayed excellent antifungal activity.To further improve their antifungal activity,benzene moiety of compound B3,B5 and B8 was introduced with different substituent groups.In the whole experiment 36 benzoic-thiazolyl ester derivatives were synthesized.Among all the compounds,compound B8 displayed excellent antifungal activity against Botrytis cinerea and Sclerotinia scleotiorum,with EC₅₀ values of 13.82 and 3.66 mg/L respectively,and slightly lower antifungal activity compared to the best compound in the experiment A.The research aimed at discovery of a novel thiazole compound with remarkable antifungal activity.The experimental results indicated that compounds A3,A15 and A24 are promising antifungal candidates worthy of further agricultural fungicide development due to their prominent effectiveness toward plant pathogenic fungi.